JP2010529971A - New microbicide - Google Patents

Abstract

【選択図】なしCompounds of formula (I) in which the substituents are as defined in claim 1 are suitable as microbicides.

[Selection figure] None

Description

  The present invention relates to novel thienyl / benzothienylethylamides having microbicidal activity, in particular fungicidal activity. Furthermore, intermediates used in the preparation of these compounds, compositions comprising these compounds and their use in agriculture and horticulture to control or prevent plant infection by phytopathogenic microorganisms, especially fungi. .

  Thienylethylamides and their use as fungicides are described in WO 2006/108791 and EP-1710237A1. Benzothienylethylamides and their use as fungicides are described in WO 2007/006739.

  It has been discovered that novel thienyl / benzothienylethylamides have microbicidal activity. Thus, the present invention provides a compound of formula I

[In the above formula,
A is a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms, each independently selected from oxygen, nitrogen and sulfur, or a phenyl ring; said heterocycle or phenyl ring is a group R ₆ , R ₇ and R ₈ ;
R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, cyano, nitro, C _1-4 alkyl, C _1-4 halogen alkyl, C _1-4 halogen alkoxy, C _1-4 alkyl (C _{1- 4} ) alkyl or C _1-4 halogenalkoxy (C _1-4 ) alkyl, provided that at least one of R ₆ , R ₇ and R ₈ is not hydrogen;
R ₁ and R ₂ independently of one another represent hydrogen, halogen, C _1-4 alkyl or C _1-4 halogenalkyl;
Q is Q ₁

であるか、又はＱはＱ₂

Or Q is Q ₂

であり；

Is;

Where R ₃ is halogen or C ₁ -C ₄ halogenalkyl;
R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl, halogen phenyl acetylinyl or halogen phenyl;
R ₅ is hydrogen, halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, phenyl, halogen phenyl, C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl or halogen phenyl acetylinyl;
R ₁₅ is hydrogen or C ₃ -C ₇ cycloalkyl.
And tautomers / isomers / enantiomers of these compounds.

According to the invention, the term “acetinyl” when used in the definition of the substituents R ₄ and R ₅ represents the group “—C≡C—”. As an example, C ₃ cycloalkylacetinyl is a group

を表し、そして例えば化合物1.1中の置換基Ｒ₄として存在する。

And is present, for example, as substituent R ₄ in compound 1.1.

  Alkyl groups in the definition of substituents can be linear or branched and include, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, n-butyl. Sec-butyl, isobutyl or tert-butyl. Alkoxy, alkenyl and alkynyl groups are derived from the mentioned alkyl groups. Alkenyl and alkynyl groups can be monounsaturated or diunsaturated.

  A cycloalkyl group in the definition of substituent is, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

  Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine. This applies correspondingly to other meanings, such as halogen in combination with halogenalkyl or halogenalkoxy.

  The halogenalkyl group preferably has a chain length of 1 to 4 carbon atoms. Halogenalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1 -Difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl And dichlorofluoromethyl.

  Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy; preferably methoxy and ethoxy. Halogen alkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2, 2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.

  Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.

  Halogen phenyl is preferably phenyl substituted by 1, 2 or 3 halogen atoms, for example 4-chlorophenyl.

  Within the scope of the present invention, “a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulfur” is preferably pyrazolyl (especially pyrazole-4 -Yl), thiazolyl (especially thiazol-5-yl), pyrrolyl (especially pyrrol-3-yl), 1,2,3-triazolyl, oxazolyl (especially oxazol-5-yl), pyridyl (especially pyrida-3-yl) ) Or 2,3-dihydro- [1,4] oxathiinyl (especially 2,3-dihydro- [1,4] oxathin-5-yl).

Compounds of formula I in which R ₁₅ is hydrogen can exist in different isomeric forms; the present invention includes all of those isomers and mixtures thereof. Compounds of formula I may exist as different tautomers. For example, compounds of formula I exist as tautomers I _I and I _II .

  The present invention includes all of these tautomers and mixtures thereof.

Preferably R ₁₅ is hydrogen. In a preferred group of compounds, A is a 5-membered heterocycle containing 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulfur; the heterocycle is a group R ₆ , R ₇ and R _8. Has been replaced by

Within the preferred group of compounds, more preferably A is A _1.

[Wherein R ₁₆ is halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C It is ₁ -C ₄ -haloalkoxy -C ₁ -C ₄ alkyl;
R ₁₇ is C ₁ -C ₄ alkyl, C ₁ -C ₄ halogenalkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C ₄ halogen alkoxy-C _1. it is -C ₄ alkyl; and R ₁₈ is hydrogen, halogen or cyano];

Or A is A ₂

[Wherein R ₂₆ is halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkoxy-C ₁ -C ₄ alkyl; and R ₂₇ is C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy- C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkoxy-C ₁ -C ₄ alkyl];

Or A is A ₃

[Wherein R ₃₆ is halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C It is ₁ -C ₄ -haloalkoxy -C ₁ -C ₄ alkyl;
R ₃₇ is C ₁ -C ₄ alkyl, C ₁ -C ₄ halogenalkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C ₄ halogen alkoxy-C _1. it is -C ₄ alkyl; and R ₃₈ represents hydrogen, halogen or cyano];

Or A is A ₄

[Wherein R ₄₆ and R ₄₇ are independently of each other halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ is -C ₄ alkyl or C ₁ -C ₄ -haloalkoxy -C ₁ -C ₄ alkyl].

In the preferable group of compounds, A is preferably A ₁ .
Within said preferred group of compounds, further preferably A is A _2.
In the preferable group of compounds, A is more preferably A ₃ .
In the preferable group of compounds, A is more preferably A ₄ .

In another preferred group of compounds, A is a phenyl ring or a 6-membered heterocycle containing 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulfur; said phenyl ring or heterocycle is a group Substituted by R ₆ , R ₇ and R ₈ .

Among the preferred compound groups, more preferably A is A _5.

(Wherein R ₅₆ is halogen, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ -haloalkoxy or C ₁ -C ₄ -haloalkoxy -C ₁ -C ₄ alkyl); and

Or A is A ₆

Wherein R ₆₆ is halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C ₄ halogen alkoxy-C be ₁ -C ₄ alkyl);

Or A is A ₇

Where R ₇₆ is C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkyl.

Within said preferred group of compounds, still more preferably from A ₅ A is.
In the preferable group of compounds, A is preferably A ₆ .
Among the preferred compound groups, more preferably A is A ₇ .

In a particularly preferred group of compounds, A is A ₁ and R ₁₈ is hydrogen. In another particularly preferred group of compounds, A is A ₁ and R ₁₆ is C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkyl, preferably C ₁ -C ₄ halogenalkyl; R ₁₇ is C ₁ it is -C ₄ alkyl; and R ₁₈ is hydrogen or halogen, preferably hydrogen.

In yet another particularly preferred group of compounds, A is A ₂ , R ₂₆ is C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkyl; and R ₂₇ is C ₁ -C ₄ alkyl.
In yet another particularly preferred group of compounds, A is A ₃ and R ₃₆ is C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkyl; R ₃₇ is C ₁ -C ₄ alkyl; and R ₃₈ is hydrogen or halogen.

In yet another particularly preferred group of compounds, A is A ₄ , R ₄₆ is C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkyl; and R ₄₇ is C ₁ -C ₄ alkyl.
In yet another particularly preferred group of compounds, A is A ₄ , R ₄₆ is halogenmethyl, preferably R ₄₆ is selected from CF ₃ , CF ₂ H and CFH ₂ ; and R ₄₇ is C ₁ -C ₄ alkyl.

In yet another particularly preferred group of compounds, A is A ₅ and R ₅₆ is halogen or C ₁ -C ₄ halogenalkyl.
In yet another particularly preferred group of compounds, A is A ₆ and R ₆₆ is halogen or C ₁ -C ₄ halogenalkyl.

In yet another particularly preferred group of compounds, A is A ₇ and R ₇₆ is C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkyl.
In a preferred group of compounds, R ₁ is hydrogen or methyl. In one aspect, R ₁ is hydrogen. In one aspect, R ₁ is methyl.
In a preferred group of compounds, R ₂ is hydrogen.

In one aspect, Q is Q ₁ .

In one aspect, Q ₁ is Q _1A

（ここでＲ₃，Ｒ₄及びＲ₅は式Ｉのもとで定義した通りである）である。この態様の中の更により好ましい化合物では、Ｒ₃はハロゲン、より好ましくはクロロ又はブロモであり；Ｒ₄はＣ₃〜Ｃ₇シクロアルキルアセチニル、フェニルアセチニル、ハロゲンフェニルアセチニル又はハロゲンフェニルであり；そしてＲ₅は水素である。それらの化合物は第１表〜第６表に与えられる。 Where R ₃ , R ₄ and R ₅ are as defined under Formula I.
Preferably, Q _1A is Q _1A-1

Where R ₃ , R ₄ and R ₅ are as defined under Formula I. In an even more preferred compound within this embodiment, R ₃ is halogen, more preferably chloro or bromo; R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl, halogen phenyl acetylinyl or halogen phenyl. Yes; and R ₅ is hydrogen. Those compounds are given in Tables 1-6.

（ここでＲ₃，Ｒ₄及びＲ₅は式Ｉのもとで定義した通りである）である。 In one aspect, Q ₁ is Q _1B

Where R ₃ , R ₄ and R ₅ are as defined under Formula I.

（ここでＲ₃，Ｒ₄及びＲ₅は式Ｉのもとで定義した通りである）である。 Preferably, Q _1B is Q _1B-1

Where R ₃ , R ₄ and R ₅ are as defined under Formula I.

（ここでＲ₃，Ｒ₄及びＲ₅は式Ｉのもとで定義した通りである）である。 Preferably, Q _1B is Q _1B-2

Where R ₃ , R ₄ and R ₅ are as defined under Formula I.

In an even more preferred compound within this embodiment, R ₃ is halogen, more preferably chloro; R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl, halogen phenyl acetylinyl or halogen phenyl; R ₅ is halogen, more preferably chloro. Those compounds are given in Tables 7-12.

（ここでＲ₃，Ｒ₄及びＲ₅は式Ｉのもとで定義した通りである）である。 Preferably, Q _1B is Q _1B-3

Where R ₃ , R ₄ and R ₅ are as defined under Formula I.

In an even more preferred compound within this embodiment, R ₃ is halogen, more preferably chloro; R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl, halogen phenyl acetylinyl or halogen phenyl; R ₅ is halogen, more preferably chloro. Those compounds are given in Tables 7-12.

In one aspect Q is Q _2. This embodiment is represented by the compounds in Tables 13 and 14.

R ₃ is preferably halogen, more preferably chloro or bromo.

In a preferred group of compounds, R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl or halogen phenyl acetylinyl.
In another preferred group of compounds, R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl.

In another preferred group of compounds, R ₄ is halogenphenylacetinyl, more preferably 4-halogenphenyl.
In yet another preferred group of compounds, R ₄ is halogenphenyl, more preferably 4-halogenphenyl.

R ₅ is preferably hydrogen or halogen.
In one aspect, R ₅ is hydrogen.
In another embodiment, R ₅ is halogen, preferably chloro.

Compounds of formula I wherein Q is Q _1A and R ₂ , R ₅ and R ₁₅ are hydrogen are prepared according to Scheme I.

Scheme I:

R ₃ is a thiophene-2-aldehyde of formula VII are as defined under formula I, R ₁ is a nitroalkane of the formula R ₁ CH ₂ NO ₂ are as defined under formula I reaction To form a nitroalkene of formula VI where R ₁ and R ₃ are as defined under formula I. The reaction is conveniently performed at a temperature between ambient and reflux in the presence of acetic acid and ammonium acetate.

The nitroalkene of formula VI can be reduced to an amine of formula V where R ₁ and R ₃ are as defined under formula I using LiAlH ₄ in an ether solvent such as diethyl ether or tetrahydrofuran. it can.

The amine of formula V can subsequently be brominated, for example with bromine in the presence of acetic acid, to an amine of formula IIIA where R ₁ and R ₃ are as defined under formula I.

The brominated amine of formula IIIA is then amidated by using the corresponding acid derivative, for example an acid chloride of formula A-C (O) Cl, where A is as defined under formula I, to give the formula The brominated amide of IIA (A, R ₁ and R ₃ are as defined under formula I) can be formed. Said amidation is carried out in the presence of a base such as triethylamine, Hunig base, sodium bicarbonate, sodium carbonate, potassium carbonate, pyridine or quinoline, preferably triethylamine, and a solvent such as diethyl ether, TBME, THF, dichloromethane, chloroform, Conveniently carried out in DMF or NMP for 10 minutes to 48 hours, preferably 12 to 24 hours, 0 ° C. to reflux temperature, preferably 20 to 25 ° C.

  The compound of formula IA can be converted to a brominated amine of formula IIA using the well-known Suzuki coupling methodology, wherein X is a halogen and n is 1, 2, 3, 4 or 5, preferably 1. It can be prepared by reacting with a compound of formula VIA. The Suzuki reaction has become one of the standard methods for direct coupling of two aromatic ring systems, for example, Journal of the Chemical Society 121 (41), 9550 (1999) and Journal fur Praktische Chemie 342 (4), 334-339 (2000).

The compound of formula IB is converted to a brominated amine of formula IIA using the well-known Sonogashira coupling methodology, using an acetylinyl compound of formula IVB, where R ^* is C ₃ -C ₇ cycloalkyl, phenyl or halogen phenyl. ). The Sonogashira reaction has become one of the standard methods for introducing alkynyl functionality into unsaturated aromatic or heteroaromatic molecules. For example, Handbook of Organopalladium Chemistry for Organic Synthesis Vol. 1, 767-789 (2002); Organocopper reagents by IB Campbell (IRL-Press, 1994); KC Nicolaou et al., Angelwandte Chemie Int. Ed., 44, 4442 (2005 R. Tykwinski et al., Ibid., 42, 1433 (2002); and A. Zapf et al., Topics in Catalysis, 19, 101 (2002).

Compounds of formula I wherein Q is Q _1B , R ₂ is hydrogen and R ₅ is chloro can be prepared according to Scheme 2.

Scheme 2:

Thiophene-3-aldehyde (compound of formula XI) can be chlorinated thoroughly with Cl ₂ / AlCl ₃ according to known methods to produce the trichlorinated thiophene aldehyde of formula X.

The compound of formula X, R ₁ can be reacted with nitroalkane of the formula R ₁ CH ₂ NO ₂ are as defined under formula I, R ₁ is as defined under formula I wherein IX nitroalkenes can be produced. The nitroalkene of formula IX can be reduced to the dichlorinated amines of formula VIIIC and VIIID where R ₁ is as defined under formula I. The amines of formula VIIIC and VIIID can then be brominated to produce amines of formula IIIC and IIID where R ₁ is as defined under formula I.

Brominated amines of formula IIIC and IIID are then amidated using the corresponding acid derivative, for example an acid chloride of formula AC (O) Cl (wherein A is as defined under formula I). By doing so, brominated amides of formula IIC and IID can be generated, wherein A, R ₁ and R ₃ are as defined under formula I.

  Compounds of formula IC and ID can be converted to brominated amines of formula IIC and IID by Suzuki reaction, wherein compound of formula VIA (where X is halogen and n is 1, 2, 3, 4 or 5, preferably Is 1).

  Suitable reaction conditions for the formation of compounds of formula VIIIC, VIIID, IIIC, IIID, IIC, IID, IC and ID are as described for Scheme 1 above.

（式中、Ａ及びＲ₁は式Ｉのもとで定義した通りであり；そしてＲ^*はＣ₃〜Ｃ₇シクロアルキル、フェニル又はハロゲンフェニルである）
は、上記スキーム１について記載されたように、ソノガシラ反応により式IIC及びIIDの化合物から生成することができる。 Compounds of formula IE and IF

Where A and R ₁ are as defined under formula I; and R ^* is C ₃ -C ₇ cycloalkyl, phenyl or halogen phenyl.
Can be generated from compounds of formula IIC and IID by the Sonogashira reaction as described for Scheme 1 above.

Compounds of formula I wherein Q is Q ₂ , R ₂ is hydrogen and R ₃ is chloro can be prepared according to Scheme 3.

Scheme 3:

The benzothiophene of formula XIII, where R ₅ is as defined under formula I, can be prepared as described in J. Org. Chem. 1996, 61 (9), 6523-25, where R ₅ is of formula I Can be prepared from the compound of formula XIV as defined under.

Starting from a benzothiophene of formula XIII, the compounds of formula XII, IIIG and IIG, where A, R ₁ and R ₅ are as defined under formula I, are prepared as described above for scheme 1. it can.

  Compounds of formula IG can be prepared by reacting a brominated amide of formula IIG with a compound of formula VIA or VIB by Suzuki reaction or Sonogashira reaction as described above for Scheme 1.

Formula VII substituent is as described above, IVA, IVB, compounds of XI and XIV, and nitroalkanes of the formula R ₁ CH ₂ NO ₂ R ₁ is as defined under formula I, known Are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.

  Compounds of the formula AC (O) Cl are known and some are commercially available. They are for example in WO 00/09482, WO 02/38542, WO 04/018438, EP-0-589-301, WO 93/11117 and Arch. Pharm. Res. 2000, 23 (4), 315-323. It can be prepared in the same way as described.

Compounds of formula I wherein R ₁₅ is C ₃ -C ₇ cycloalkyl can be prepared, for example, according to the following reaction scheme.

To prepare all further compounds of formula I functionalized according to the definitions of A, Q, R ₁ and R ₂ , a number of suitable known standard methods such as alkylation, halogenation, acylation, amidation There are oximation, oxidation and reduction methods. The selection of a suitable preparation method depends on the nature (reactivity) of the substituents in the intermediate.

  The reaction to provide the compound of formula I is advantageously carried out in an aprotic inert organic solvent. Such solvents are hydrocarbons such as benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene, ethers such as diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane. Nitriles such as acetonitrile or propionitrile, amides such as N, N-dimethylformamide, diethylformamide or N-methylpyrrolidinone. The reaction temperature is preferably from -20 ° C to + 120 ° C. In general, the reactions are slightly exothermic and generally they can be carried out at room temperature. In order to shorten the reaction time or to initiate the reaction, the mixture can be heated briefly to the boiling point of the reaction mixture. The reaction time can also be shortened by adding a few drops of base as a reaction catalyst. Suitable bases are in particular tertiary amines such as trimethylamine, triethylamine, quinuclidine, 1,4-diazabicyclo [2.2.2] octane, 1,5-diazabicyclo [4.3.0] non-5-ene. Or 1,5-diazabicyclo [5.4.0] undec-7-ene. However, inorganic bases such as hydrides such as sodium or calcium hydride, hydroxides such as sodium or potassium hydroxide, carbonates such as sodium carbonate and potassium carbonate, or bicarbonates such as potassium bicarbonate And sodium bicarbonate may be used as the base.

  The base can be used alone or with a catalytic amount of a phase transfer catalyst such as a crown ether, especially 18-crown-6, or a tetraalkylammonium salt.

  The compound of formula I is isolated in a conventional manner by concentrating and / or evaporating the solvent and recrystallized in a solvent in which the solid residue is not readily soluble, such as ethers, aromatic hydrocarbons or chlorinated hydrocarbons Or it can refine | purify by grind | pulverizing.

  The compounds of formula I and, if appropriate, their tautomers, depend on the number, absolute and relative configuration of the asymmetric carbon atoms present in the molecule and / or are non-aromatic double bonds present in the molecule. Depending on the configuration of the bonds, it can exist in one form of possible isomers or as a mixture thereof, for example in the form of pure isomers, such as antipodes and / or diastereomers, or isomers It can exist as a mixture, for example an enantiomeric mixture, for example a racemate, a diastereomeric mixture or a racemic mixture; the invention also relates to the pure isomers and all possible isomer mixtures and in each case Even if stereochemical details are not specifically mentioned in the above, they should be construed in the text above and below.

  Compound I and, if appropriate, its tautomer may also be obtained in the form of a hydrate if appropriate and / or used for crystallization of the compound present in another solvent, for example in solid form. Solvents that can also be included.

  The compounds of formula I according to the invention have been found for practical purposes to have a very advantageous spectrum of activity to protect useful plants against diseases caused by phytopathogenic microorganisms such as fungi, bacteria or viruses. It was done.

  The present invention relates to a method for controlling or preventing infection of useful plants by phytopathogenic microorganisms, wherein the compound of formula I is applied as an active ingredient to a plant, to a plant part or to its location. The compounds of formula I according to the invention are distinguished by excellent activity at low application rates, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are useful for protecting a large number of useful plants. The compounds of formula I inhibit or repel diseases that occur on plants of various crops of useful plants or on parts of plants (fruits, flowers, leaves, stems, tubers, roots) and at the same time of plants that grow later The moiety can also be used, for example, to protect against phytopathogenic microorganisms.

  Dressing for the treatment of plant propagation materials, especially seeds (fruit, tubers, grains) and plant cuttings (eg rice) to protect against fungal infection and against phytopathogenic fungi present in the soil It is also possible to use compounds of the formula I as

  Furthermore, the compounds of the formula I according to the invention can be used for controlling fungi in the relevant fields, for example in the protection of technical materials including wood and wood-related technical products, food storage or hygiene management.

  The compounds of formula I are effective, for example, against the following classes of phytopathogenic fungi: imperfect fungi [for example Botrytis, Pyricularia, Helminthosporium, Fusarium ), Septoria, Cercospora and Alternaria] and basidiomycetes (eg Rhizoctonia, Hemileia, Puccinia), in addition to the Ascomycetes class (eg Venturia). Also effective against (Venturia), Erysiphe, Podosphaera, Monilinia, Uncinula) and Oomycetes (eg Phytophthora, Pythium, Plasmopara) Significant activity was observed against powdery mildew (Ericife sp.). The novel compounds of formula I are effective against phytopathogenic bacteria and viruses (eg against Xanthomonas, Pseudomonas, Erwinia amylovora and tobacco mosaic virus). is there.

  Useful plants that can be protected within the scope of the present invention typically comprise the following plant species: cereals (wheat, barley, rye, oats, rice, corn, sorghum and related species). Beets (sugar beet and feed beets); berries, stones and soft fruits (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); legumes (peas, lentils) Oil plant (rape, mustard, poppy, olive, sunflower, palm, castor oil plant, cacao bean, peanut); cucumber family plant (pumpkin, cucumber, melon); fiber plant (cotton, flax, Hemp, jute); citrus (orange, lemon, grapefruit, mandarin); vegetables (spinach, lettuce, asparagus, cabbage, carrot, tama Leeks, tomatoes, potatoes, peppers); camphoraceae (avocado, cinnamon, camphor) or plants such as tobacco, nuts, coffee, eggplant, sugarcane, tea, pepper, vine, hops, bananas and natural rubber and houseplants.

  The term “useful plant” refers to a herbicide or herbicide class such as bromoxynil [eg HPPD herbicides, ALS inhibitors such as primsulfuron, prosulfuron and trifloxysulfuron as a result of routine methods of breeding or genetic manipulation. , EPSPS (5-enolpyrovir-shikimate-3-phosphate synthase) inhibitor, GS (glutamine synthase) inhibitor or PPO (protoporphinogen oxidase) inhibitor] useful plants are also included It should be understood as something to do. An example of a crop that has been rendered tolerant to imidazolinones, such as imazamox, by routine breeding methods (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been made resistant to herbicides or to the class of herbicides by genetic engineering include the trade names RoundupReady (R), Herculex I (R) and LibertyLink (R). Commercially available glyphosate and glufosinate resistant corn varieties can be mentioned.

  The term “useful plant” is capable of synthesizing one or more selectively active toxins, eg useful plants that can be synthesized, known from toxin-producing bacteria, in particular those of the genus Bacillus, recombinant DNA It should also be construed to include useful plants that have been transformed by use of the technique.

  The term “useful plant” refers to a recombinant DNA capable of synthesizing anti-phytopathogenic substances having a selective action, such as so-called “pathogenic proteins” (see PRP, eg EP-A-0 392 225). It should also be construed to include useful plants that have been transformed by use of the technique. Examples of such anti-pathogenic substances and transgenic plants capable of synthesizing such anti-pathogenic substances are for example EP-A-0 392 225, WO 95/33818 and EP-A-0 353 191. Methods for producing such transgenic plants are widely known to those skilled in the art and are described, for example, in the publications mentioned above.

  As used herein, the term “location” of a useful plant refers to the location where the useful plant is growing, the location where the plant propagation material of the useful plant is sown, or the plant propagation material of the useful plant is sown in the soil. It includes the place where it will be. An example of such a place is a field where crops are growing.

The term “plant propagation material” is understood to denote a reproductive part of a plant, for example seeds that can be used for the propagation of the latter, and plant material, for example cuttings or tubers, for example potatoes. Examples include seeds (strictly speaking), roots, fruits, tubers, bulbs, rhizomes and plant parts. Reference can also be made to germinated plants and seedlings that are to be transplanted after germination or emerged from the soil. These seedlings can be protected before transplantation by complete or partial treatment by immersion. Preferably “plant propagation material” is understood to represent seed.

  The compounds of formula I can be used in unmodified form or preferably together with carriers and auxiliaries usually used in the pharmaceutical field.

  Accordingly, the present invention comprises a composition for controlling and protecting against phytopathogenic microorganisms comprising a compound of formula I and an inert carrier, and controlling or preventing infection of useful plants by phytopathogenic microorganisms With regard to the method, the composition comprising a compound of formula I as active ingredient and an inert carrier is applied to the plant, to the plant part or to its location.

  To that end, the compounds of formula I and inert carriers are conveniently prepared in a known manner as emulsions, coating pastes, directly sprayable or dilutable solutions, diluted emulsions, wettable powders, soluble powders, powders, granules. And formulated into capsules, for example, capsules in heavy synthetic materials. According to the form of the composition, the method of application, for example the method of spraying, spraying, dressing, dispersing, coating or pouring is selected according to the intended purpose and general circumstances. The composition may contain additional adjuvants such as stabilizers, antifoams, viscosity modifiers, binders or tackifiers and fertilizers, micronutrient supplies, or other formulations for special effects.

  Suitable carriers and adjuvants can be solid or liquid and are useful in formulation technology, such as natural or regenerated inorganic materials, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or It is fertilizer. Such carriers are for example described in WO 97/33890.

  A composition comprising a compound of formula I or a compound of formula I as an active ingredient and an inert carrier may be applied to the plant site or plant to be treated simultaneously or sequentially with the additional compound. it can. These additional compounds can be, for example, fertilizers or micronutrient donations or other formulations that affect plant growth. They are selective herbicides as well as insecticides, fungicides, fungicides, nematicides, if desired, together with additional carriers, surfactants or application aids commonly used in the field of formulation. It can also be a molluscicide or a mixture of these formulations.

  A preferred method of applying a composition comprising a compound of formula I or a compound of formula I as an active ingredient and an inert carrier is foliar application. The frequency and amount of application will depend on the risk of infection with the corresponding pathogen. However, the compounds of formula I can be planted through the roots from the soil by dipping the plant site in a liquid formulation (systemic action) or by applying solid compounds, eg granular compounds, to the soil (soil application). Can penetrate. In paddy rice crops, such granules can be sprayed on flooded paddy fields. The compounds of formula I can also be applied (coated) by immersing the seeds or tubers in a liquid formulation of a fungicide or by coating them with a solid formulation.

  Formulations, i.e. compositions comprising a compound of formula I and optionally a solid or liquid adjuvant, are prepared in a known manner, typically by adding the compound to a bulking agent such as a solvent, a solid carrier, and optionally a surfactant. Prepared by thorough mixing and / or grinding with compound (surfactant).

  Agrochemical formulations are typically 0.1-99% by weight, preferably 0.1-95% by weight of the compound of formula I, 99.9-1% by weight, preferably 99.8-5% by weight solid or liquid adjuvant, and 0-25% by weight. Preferably 0.1 to 25% by weight of surfactant.

  If it is preferred to formulate the product as a concentrate, the end user will generally use a diluted formulation.

  Advantageous application rates are usually 5 g to 2 kg active ingredient (a.i.) per hectare (ha), preferably 10 g to 1 kg a.i./ha, most preferably 20 g to 600 g a.i./ha. When used as a seed soaking agent, a convenient application rate is 10 mg to 1 g of active substance per kg of seed. The application rate for the desired action can be determined by experiment. It depends, for example, on the mode of action, the stage of development of the useful plant, and the application (location, time, method of application) and can vary within wide limits due to their parameters.

  Surprisingly, the compounds of formula I are useful in methods of protecting plant crops against attack by phytopathogenic organisms, and the combination of glyphosate and at least one compound of formula I to plants or in place It has been discovered that can be used in a method for treating crops of useful plants infected with phytopathogenic organisms, wherein the plant is resistant or sensitive to glyphosate.

  The method can provide unexpectedly improved disease control compared to using a compound of formula I in the absence of glyphosate. Said method may be effective to enhance disease control by compounds of formula I. It is already known that a mixture of glyphosate and at least one compound of formula I can at least partially increase the disease spectrum controlled by the compound of formula I while being controlled to some extent by the compound of formula I. An increase in the activity of the compounds of formula I against the diseased species being observed can also be an observed effect.

  The method is particularly effective against phytopathogenic organisms of the fungi genus Basidiomycota, Rust fungi, Rust subclass Rustaceae (commonly referred to as Rust fungi). The species of rust fungi that are particularly damaging to agriculture include the Facospora family, especially those of the genus Facopsora, such as Phakopsora pachyrhizi (also called Asian soybean rust fungi), and those of the Paxinaceae family, Especially those belonging to the genus Paxinia, such as Puccinia graminis (also known as rust fungus or black rust fungus, which is a problem in cereal crops), and Puccinia recondita (as red rust fungus) Also known).

  One aspect of the method is a method for protecting crops of useful plants against attack by phytopathogenic organisms and / or treating crops of useful plants infected with phytopathogenic organisms, the methods comprising plants, plant parts and Applying simultaneously to at least one selected from the group consisting of plant locations, glyphosate, including salts or esters, and at least one compound of formula I having activity against phytopathogenic organisms .

  The compounds of formula (I) described above or pharmaceutically acceptable salts thereof also have an activity spectrum that is advantageous for the treatment and / or prevention of microbial infections in animals.

  An “animal” can be any animal, such as insects, mammals, reptiles, fish, amphibians, preferably mammals, most preferably humans. “Treatment” means the use of an animal with a microbial infection to reduce or delay or stop the increase or spread of infection, or to reduce infection or treat infection. “Prevention” means use on animals that have no obvious signs of microbial infection, either to prevent any future infection or to reduce or delay the increase or transmission of any future infection.

  According to the present invention there is provided the use of a compound of formula (I) in the manufacture of a medicament for use in the treatment and / or prevention of microbial infections in animals. Also provided is the use of a compound of formula (I) as a medicament. Also provided is the use of a compound of formula (I) as an antibacterial agent in the treatment of animals. According to the present invention there is also provided a pharmaceutical composition comprising a compound of formula (I) as an active ingredient or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier. This composition can be used for the treatment and / or prevention of microbial infections in animals. The pharmaceutical composition should be in a form suitable for oral administration such as tablets, lozenges, hard capsules, aqueous suspensions, oily suspensions, emulsions, dispersible powders, dispersible granules, syrups and elixirs. Can do. Alternatively, the pharmaceutical composition can be in a form suitable for topical application, such as a spray, cream or lotion. Alternatively, the pharmaceutical composition can be in a form suitable for parenteral administration, such as an injection. Alternatively, the pharmaceutical composition can be in inhaled form, for example an aerosol spray.

  The compounds of formula (I) are effective against various microbial species that can cause microbial infections in animals. Examples of such microbial species include those that cause aspergillosis, such as Aspergillus fumigatus, A. et al. A. flavus, A. flavus A. terrus, A. terrus A. nidulans and A. nidulans A. niger; those that cause blastosis, such as Blastomyces dermatitidis; those that cause candidiasis, such as Candida albicans, C.I. C. glabrata, C.I. C. tropicalis, C.I. C. parapsilosis, C.I. C. krusei and C.I. C. lusitaniae; those that cause coccidioidomycosis, such as Coccidioides immitis; those that cause cryptococcosis, such as Cryptococcus neoformans; those that cause histoplasmosis, such as Hystoplasma capsulatum; and those that cause zygomycosis, such as Apsidia corymbifera, Rhizomucor pusillus and Rhizopus arrhizus. Further examples are Fusarium species such as Fusarium oxysporum and Fusarium solani and Sedosporum species such as Scedosporium apiospermum and Scedosporium prolicosium prosificum (Scedo). Further examples are Mycrosporum species, Trichophyton species, Epidermophyton species, Mucor species, Sporothorix species, Fiarophora species (Phialophora) species, Cladosporium species, Petriellidium species, Paracoccidioides species and Histoplasma.

The following non-limiting examples illustrate the invention in more detail without limitation.
Preparation example
Example P1: 3-Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2- (3-chloro-5-cyclopropylethynylthiophen-2-yl) -1-methylethyl] amide (Compound 1.26) Preparation of

240 mg (0.58 mmol) 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2- (5-bromo-3-chlorothiophen-2-yl) -1-methyl in a sulfonation flask Ethyl] amide, 80 mg (1.15 mmol) cyclopropylacetylene, 10 mg copper (I) iodide, 36 mg (0.05 mmol) bistriphenylphosphine dichloride and 30 mL triethylamine at 60 ° C. For 2 days. Another 80 mg of cyclopropylacetylene was then added and stirring was continued for 24 hours. After cooling to ambient temperature, ethyl acetate and water were added and the organic layer was separated and rewashed twice with water. After drying (sodium sulfate) and evaporating the solvent under water stream vacuum, the crude product was obtained. Purification was carried out by column chromatography over silica gel (eluent: ethyl acetate / heptane 1: 1). Yield: 90 mg (23% of theory) of slightly brown resin ( ¹ H-NMR: 0.8 / m / 2H, 0.9 / m / 2H, 1.22 / d / 3H, 1.45 / m / 1H, 3.01 / d / 2H, 3.9 / s / 3H, 4.40 / m / 1H, 6.28 / s (wide) / 1H, 6.88 / t / 1H-CF ₂ H, 6.89 / s / 1H, 7.85 / s / 1H).

Example P2: 3-Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid {2- [3-chloro-5- (4-fluorophenyl) thiophen-2-yl] -1-methylethyl} amide Preparation of (Compound 1.46)

207 mg (0.5 mmol) of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2- (5-bromo-3-chlorothiophen-2-yl) -1-methyl in a sulfonation flask Ethyl] amide, 90 mg (0.64 mmol) 4-fluorophenylboronic acid, 151 mg (1.8 mmol) sodium bicarbonate, 36 mg (0.05 mmol) bistriphenylphosphine palladium dichloride, 10 mL dimethoxyethane and 5 The mixture containing mL of water was stirred at reflux temperature for 6 hours. After cooling to ambient temperature, ethyl acetate and water were added and the organic layer was separated and rewashed twice with water. The crude product was obtained after drying (sodium sulfate) and distillation of the solvent under water flow vacuum. Purification was carried out by column chromatography over silica gel (eluent: ethyl acetate / heptane 1: 1). Yield: 180 mg (80% of theory) of a slightly brown oil ( ¹ H-NMR: 1.29 / d / 3H, 0.9 / m / 2H, 3.09 / m / 2H, 3.89 / s / 3H, 4.42 / m / 1H, 6.38 / s (wide) / 1H, 6.89 / t / 1H-CF ₂ H, 7.05 / m / 2H, 7.48 / m / 2H, 7.89 / s / 1H).

Example P3: 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid {2- [2,4-dichloro-5- (4-fluorophenyl) thiophen-3-yl] -1-methyl Ethyl} amide (compound 7.70) and 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid {2- [4,5-dichloro-2- (4-fluorophenyl) thiophen-3-yl] Preparation of -1-methylethyl} amide (Compound 7.72)

280 mg (0.6 mmol) of the isomeric amide mixture obtained in Example P5c) in a sulfonation flask was dissolved in 10 mL of 1,2-dimethoxyethane. Add 105 mg (0.75 mmol) 4-fluorophenylboronic acid, 35 mg (0.05 mmol) bis (triphenylphosphine) palladium dichloride and 225 mg (2.7 mmol) sodium bicarbonate dissolved in 5 mL water The resulting mixture was stirred at 70-75 ° C. for 3 hours. After cooling, 100 mL of water was added and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with brine to give a crude mixture of isomers after drying (sodium sulfate) and evaporation of the solvent. The first purification was performed by column chromatography on silica gel (eluent: ethyl acetate / heptane 1: 1). Two fluorophenyl isomers were isolated by HPLC (high pressure liquid chromatography). Regioisomer I (compound 7.70) was obtained in pure form as a colorless oil ( ¹ H-NMR: 1.31 / d / 3H, 2.9 / m / 2H (diastereotropic proton), 3.97 / s / 3H , 4.55 / m / 1H, 5.98 / d (wide) / 1H, 7.12 / t / 2H, 7.53 / m / 2H, 7.87 / s / 1H)). Regioisomer 2 (compound 7.72) could also be obtained in the pure form of white crystals (melting point 127-130 ° C.) (84 mg = 29% of theory).

Example P4: 3-Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2- (5-bromo-3-chlorothiophen-2-yl) -1-methylethyl] amide (compound Z1.2 Preparation of
a) Preparation of 3-chloro-2-((E) -nitropropenyl) thiophene

In a sulfonation flask, a mixture containing 11.7 g (0.08 mol) 3-chlorothiophene-2-carbaldehyde, 48 g (0.64 mol) nitroethane, 15.4 g (0.2 mol) ammonium acetate and 160 mL acetic acid was added. Heated at 90 ° C. for 5 hours. After cooling, ethyl acetate was added and the organic phase was washed 3 times with water. After drying the organic phase over sodium sulfate and filtering, the organic solvent was distilled off under a water stream vacuum. The residue was purified by column chromatography over silica gel (eluent: ethyl acetate / heptane 1: 5). Yield: 10.8 g colorless oil (67% of ^{theory) (1 H-NMR: 2.57} / s / 3H, 7.12 / d / 1H, 7.62 / d / 1H, 8.45 / s / 1H).

b) Preparation of 2- (3-chlorothiophen-2-yl) -1-methylethylamine

In a sulfonation flask, 5.4 g (0.0265 mol) of 3-chloro-2-((E) -nitropropenyl) thiophene was added with 1M LiAlH4 (0.12 mol) so that the internal temperature was constant at 0-5 ° C. Added to 120 mL of ethereal solution. The mixture was then stirred at 20 ° C. for 4 hours. After quenching at 5 ° C. with a minimum amount of water, sodium sulfate was added. The crude product was obtained after filtration and evaporation of the solvent under water stream vacuum. Purification was carried out by column chromatography over silica gel (eluent: tert-butyl methyl ether / EtOH 3: 1). 34.6 g (74% of theory) of colorless oil ( ¹ H-NMR: 1.18 / d / 3H, 1.42 / s / NH ₂ , 2.72-2.9 / m (diastereotropic proton) / 2H, 3.25 / m / 1H, 6.89 / d / 1H, 7.16 / d / 1H).

c) Preparation of 2- (5-bromo-3-chlorothiophen-2-yl) -1-methylethylamine (Compound Z2.2)

In a sulfonation flask, 5 g (0.028 mol) of 2- (3-chlorothiophen-2-yl) -1-methylethylamine was dissolved in 70 mL of acetic acid. The mixture was then cooled to 15 ° C. and 4.8 g (0.30 mol) of bromine was added with stirring (internal temperature 15-17 ° C.). After warming to room temperature, the mixture was stirred for 16 hours. The mixture was then poured into a mixture of tert-butyl methyl ether (about 250 mL) and 2N sodium hydroxide. The final pH was 11. The crude product was obtained after washing with brine, drying over sodium sulfate and evaporation of the solvent. Purification was carried out by column chromatography over silica gel (eluent: tert-butyl methyl ether / EtOH 10: 1). Yield: 5.4 colorless oil g (75% of ^{theory) (1 H-NMR: 1.18} / d / 3H, 2.68-2.87 / m ( diastereo directional proton) / 2H, 3.2 / m / 1H, 6.87 / s / 1H).

d) of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2- (5-bromo-3-chlorothiophen-2-yl) -1-methylethyl] amide (compound Z1.2) Preparation

  In a sulfonation flask, 1 g (4 mmol) of the amine prepared in Example 3 and 1 mL (6 mmol) of triethylamine were dissolved in 30 mL of methylene chloride. A mixture of 780 mg (4 mmol) of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid chloride and 10 mL of methylene chloride was then added at room temperature with stirring. After stirring for 16 hours, the solvent was evaporated under a water-flow vacuum and the residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 1: 1). Yield: 1.65 g (83% of theory) of white crystals. Melting point 157-158 ° C.

Example P5: 3-Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2- (5-bromo-3-chlorothiophen-2-yl) -1-methylethyl] amide (compound Z1.2 Preparation of
a) Preparation of 2- (4,5-dichlorothiophen-3-yl) -1-methylethylamine and 2- (2,4-dichlorothiophen-3-yl) -1-methylethylamine

In a sulfonation flask, 10 mL (10 mmol) of 1M ethereal LiAlH ₄ was slowly added to 30 mL of tetrahydrofuran. 0.9 g (3.32 mmol) of 2,3,5-trichloro-4-((E) -2-nitropropenyl) thiophene was then added slowly so that the internal temperature was constant at 10-12 ° C. Stirring was continued at 10-12 ° C. for 3 hours. The mixture was then quenched with 0.4 mL water and 0.38 g sodium hydroxide solution (15%). After addition of 5 mL of saturated ammonium chloride solution, the suspension was filtered. The liquid phase was dried and then the solvent was distilled off in a water flow vacuum. The crude material was purified by column chromatography over silica gel (eluent: tert-butyl methyl ether / ethanol 20: 1-1: 1). The resulting amine mixture (0.4 g) was 27% 2- (4,5-dichlorothiophen-3-yl) -1-methylethylamine, 30% 2- (2,4-dichlorothiophen-3-yl) It contained -1-methylethylamine and 43% of the undesired trichloro compound 2- (2,4,5-trichlorothiophen-3-yl) -1-methylethylamine.

b) of 2- (2-bromo-4,5-dichlorothiophen-3-yl) -1-methylethylamine and 2- (5-bromo-2,4-dichlorothiophen-3-yl) -1-methylethylamine Preparation

  In a sulfonation flask, the isomer mixture obtained in 2.49 g (11.9 mmol) of Example P5a) was dissolved in 25 mL of acetic acid. Then 1.99 g (12.4 mmol) bromine was added dropwise over 5 minutes. Stirring was continued at room temperature for 16 hours and then the acid was evaporated in a stream of water. The solid residue was poured into 50 mL saturated sodium bicarbonate solution and the aqueous phase was extracted three times with tert-butyl methyl ether. After drying the organic phase (sodium sulfate) and distilling off the solvent in a water stream, the crude product was obtained. Purification was carried out by column chromatography on silica gel (eluent: tert-butyl methyl ether / ethanol 20: 1 to 1: 1). 2.1 g of brown oil was 27% 2- (2-bromo-4,5-dichlorothiophen-3-yl) -1-methylethylamine, 27% 2- (5-bromo-2,4-dichlorothiophene) -3-yl) -1-methylethylamine and 43% of undesired 2- (2,4,5-trichlorothiophen-3-yl) -1-methylethylamine.

c) 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid [2- (2-bromo-4,5-dichlorothiophen-3-yl) -1-methylethyl] amide and 1-methyl Preparation of -3-trifluoromethyl-1H-pyrazole-4-carboxylic acid [2- (5-bromo-2,4-dichlorothiophen-3-yl) -1-methylethyl] amide

    In a sulfonation flask, 2.07 g (7.2 mmol) of the amine isomer mixture prepared in Example P5b) and 1.45 g (14.4 mmol) of triethylamine were dissolved in 50 mL of methylene chloride. A mixture of 1.65 g (7.2 mmol) of 3-trifluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid chloride and 50 mL of methylene chloride was then added with stirring at room temperature. After stirring for 16 hours, the solvent was evaporated in a stream of vacuum and the residue was purified by column chromatography on silica gel (eluent: ethyl acetate / heptane 1: 2-2: 1). 1.52 g of a mixture of amide isomers was obtained in the form of slightly brown crystals (melting point 134-138 ° C.). This mixture was 27% 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid [2- (2-bromo-4,5-dichlorothiophen-3-yl) -1-methylethyl] amide. , 30% 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid [2- (5-bromo-2,4-dichlorothiophen-3-yl) -1-methylethyl] amide and 43 % Undesired 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid [2- (2,4,5-trichlorothiophen-3-yl) -1-methylethyl] amide.

Tables 1-14: Compounds of Formula I The invention is further illustrated by the preferred compounds of formula (I) listed in Tables 1-14. Characteristic data are given in Table 21.

Table 1: Compounds of formula Ia

Table 2: Compounds of formula Ib

Table 3: Compounds of formula Ic

Table 4: Compounds of formula Id

Table 5: Compounds of formula Ie

Table 6: Compounds of formula If

Table 7: Compounds of formula Ig

Table 8: Compounds of formula Ih

Table 9: Compounds of formula Ii

Table 10: Compounds of formula Ij

Table 11: Compounds of formula Ik

Table 12: Compounds of formula Il

Table 13: Compounds of formula Im

Table 14: Compounds of formula In

Tables 15-17: Compounds of Formula II The invention is further illustrated by the preferred compounds of formula (II) listed in Tables 15-17. Characteristic data are given in Table 21.

Table 15: Compounds of formula (IIa)

Table 16: Compounds of formula IIb

Table 17: Compounds of formula IIc

Tables 18-20: Compounds of Formula III The invention is further illustrated by the preferred compounds of formula (III) listed in Tables 18-20. Characteristic data are given in Table 21.

Table 18: Compounds of formula (IIIa)

Table 19: Compounds of formula IIIb

Table 20: Compounds of formula IIIc

Table 21: Characteristic data Table 21 shows specific melting points and specific NMR data for the compounds of Tables 1-20. Unless otherwise stated, CDCl ₃ was used as the solvent for NMR measurements. If a mixture of solvents is present, this is indicated for example as CDCl ₃ / d ₆ -DMSO. No attempt was made to raise all property data for the compounds in Tables 1-20. Throughout Table 21 and the description provided below, temperatures are given in degrees Celsius. “NMR” means nuclear magnetic resonance spectrum; MS stands for mass spectrum; “%” is percent by weight, unless the corresponding concentration is indicated in another unit. The following abbreviations were used throughout this specification.

mp = melting point
bp = boiling point
s = single line
br = wide d = double wire
dd = double line t = triple line q = quadruple line m = multiple line
ppm = parts per million

Table 21

Tables 1a-14: Compounds of Formula IAa The invention is further illustrated by the preferred compounds of formula (IAa) listed in Tables 1a-14a.

Table 1a: Compounds of formula IAa

Table 2a: Compounds of formula IAb

Table 3a: Compounds of formula IAc

Table 4a: Compounds of formula IAd

Table 5a: Compounds of formula IAe

Table 6a: Compounds of formula Iaf

Table 7a: Compounds of formula IAg

Table 8a: Compounds of formula IAh

Table 9a: Compounds of formula IAi

Table 10a: Compounds of formula IAj

Table 11a: Compounds of formula IAk

Table 12a: Compounds of formula IIaa

Table 13a: Compounds of formula IAm

Table 14a: Compounds of formula IAn

Tables 15a-17a: Compounds of Formula IIaaa The invention is further illustrated by the preferred compounds of formula (IIaaa) listed in Tables 15a-17a. Characteristic data is given in Table 21a.

Table 15a: Compounds of formula (IIa)

Table 16a: Compounds of formula IIab

Table 17a: Compounds of formula IIac

Tables 18a-20a: Compounds of Formula III The present invention is further illustrated by the preferred compounds of formula (III) listed in Tables 18a-20a. Characteristic data is given in Table 21a.

Table 18a: Compounds of formula (IIIaa)

Table 19a: Compounds of formula IIIab

Table 20a: Compounds of formula IIIac

Formulation examples of compounds of formula I
Examples F-1.1 to F-1.2: Concentrated emulsion

The desired concentration of emulsion can be prepared by diluting such a concentrate with water.

F-2: Concentrated emulsion

The desired concentration of emulsion can be prepared by diluting such a concentrate with water.

Examples F-3.1 to F-3.4: Solution

The solution is suitable for use in the form of microdroplets.

Examples F-4.1 to F-4.4: Granules

The new compound is dissolved in dichloromethane, the solution is sprayed onto the support and the solvent is then removed by vacuum distillation.

Examples F-5.1 and F-5.2: Powder

By thoroughly mixing all the components, a ready-to-use powder is obtained.

Examples F-6.1 to F-6.3: wettable powder

All ingredients can be mixed and the mixture can be thoroughly ground in a suitable mill to provide a wettable powder, which can be diluted with water to any desired concentration of suspension.

Example F-7: Flowable concentrate for seed treatment

  The finely divided active ingredient is thoroughly mixed with the adjuvant to give a concentrated suspension, and dilution with water can give a suspension of any desired dilution. Such diluents can be used to treat plant propagation material and protect against infection by microorganisms by spraying, irrigating or dipping.

Biological examples
Example B-1: Action against Botrytis cinerea / Tomato (Botrytis on tomato)
A 4-week-old tomato plant variety Roter Gnom was treated with a test compound formulation (0.02% active ingredient) in a spray chamber. Two days after application, it was inoculated into tomato plants by spraying a spore suspension (1 × 10 ⁵ conidia / mL) on the test plants. Disease development was assessed after an incubation period of 20 ° C. and 95% relative humidity (rh) in the growth chamber. Compounds 1.38, 7.27 and 7.38 showed good activity in this study (<20% infection).

Example B-2: Action on Uncinula necator / Grapes (Grade powdery mildew)
Five week old grape cuttings cv. Gutedel were treated with the test compound formulation (0.02% active ingredient) in a spray chamber. One day after application, plants infected with grape powdery mildew were inoculated into the grape plants by shaking on the test plants. Disease development was assessed after a 7 day incubation period at 26 ° C. and 60% rh under a photoperiod of 14/10 hours (lighting / shading). Compounds 1.38, 6.14, 7.27, 7.38, 12.6 and 12.30 showed good activity in this study (<20% infection).

Example B-3: Effect on Puccinia recondita / wheat (wheat red rust)
One week old wheat plant cv. Arina was treated with the test compound formulation (0.02% active ingredient) in a spray chamber. One day after application, wheat plants were inoculated by spraying a spore suspension (1 × 10 ⁵ conidia / mL) on the test plants. After a 2 day incubation period of 20 ° C. and 95% rh, the plants were kept in the greenhouse for 8 days at 20 ° C. and 60% rh. Disease occurrence was evaluated 10 days after inoculation. Compounds 1.38, 6.14 and 7.38 showed good activity in this study (<20% infection).

Example B-4: Effect on Septoria tritici / wheat (septria leaf spot on wheat)
Two week old wheat plant cv. Riband was treated with the test compound formulation (0.02% active ingredient) in a spray chamber. One day after application, wheat plants were inoculated by spraying a spore suspension (10 × 10 ⁵ conidia / mL) on the test plants. After a one day incubation period at 23 ° C. and 95% rh, the plants were maintained in a greenhouse at 23 ° C. and 60% rh for 16 hours. Disease occurrence was assessed 18 days after inoculation. Compounds 1.38, 6.14 and 7.38 showed good activity in this study (<20% infection).

Example B-5: Action on Pyrenophora teres / Barley (reticular spots on barley)
One week old barley plant cv. Express was treated with the test compound formulation (0.02% active ingredient) in a spray chamber. Two days after application, barley plants were inoculated by spraying a spore suspension (3 × 10 ⁴ conidia / mL) on the test plants. After a 2 day incubation period at 20 ° C. and 95% rh, the plants were kept in the greenhouse at 20 ° C. and 60% rh. Disease occurrence was assessed 4 days after inoculation. Compounds 1.38, 6.14, 7.27, 7.38, 12.6 and 12.30 showed good activity in this study (<20% infection).

Example B-6: Action against Alternaria solani / Tomato (Premature wilt on tomato)
A 4-week-old tomato plant cv. Roter Gnom was treated with the test compound formulation (0.02% active ingredient) in a spray chamber. Two days after application, tomato plants were inoculated by spraying a spore suspension (2 × 10 ⁵ conidia / mL) on the test plants. Disease development was assessed after a 3 day incubation period in a greenhouse at 20 ° C. and 95% rh. Compounds 1.38, 7.27, 7.38, 12.6 and 12.30 showed good activity in this study (<20% infection).

Claims (14)

Compound of formula I

[In the above formula,
A is a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms, each independently selected from oxygen, nitrogen and sulfur, or a phenyl ring; said heterocycle or phenyl ring is a group R ₆ , R ₇ and R ₈ ;
R ₆ , R ₇ and R ₈ are each independently hydrogen, halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy (C ₁ -C ₄ ) alkyl or C ₁ -C ₄ halogenalkoxy (C ₁ -C ₄ ) alkyl, provided that at least one of R ₆ , R ₇ and R ₈ is not hydrogen;
R ₁ and R ₂ independently of one another represent hydrogen, halogen, C ₁ -C ₄ alkyl or C ₁ -C ₄ halogen alkyl;
Q is Q ₁

Or Q is Q ₂

Is;
Where R ₃ is halogen or C ₁ -C ₄ halogenalkyl;
R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl, halogen phenyl acetylinyl or halogen phenyl;
R ₅ is hydrogen, halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, phenyl, halogen phenyl, C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl or halogen phenyl acetylinyl;
R ₁₅ is hydrogen or C ₃ -C ₇ cycloalkyl.
And tautomers / isomers / enantiomers of these compounds. 2. A compound of formula I according to claim 1, wherein _R15 is hydrogen. A is a 5-membered heterocycle containing 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulfur; said heterocycle being substituted by groups R ₆ , R ₇ and R ₈ 2. A compound of formula I according to claim 1. A is A ₁

Wherein R ₁₆ is halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C It is ₁ -C ₄ -haloalkoxy -C ₁ -C ₄ alkyl;
R ₁₇ is C ₁ -C ₄ alkyl, C ₁ -C ₄ halogenalkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C ₄ halogen alkoxy-C _1. it is -C ₄ alkyl; and R ₁₈ is hydrogen, halogen or cyano);
Or A is A ₂

Wherein R ₂₆ is halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkoxy-C ₁ -C ₄ alkyl; and R ₂₇ is C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy- C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkoxy-C ₁ -C ₄ alkyl);
Or A is A ₃

(Where R ₃₆ is halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C It is ₁ -C ₄ -haloalkoxy -C ₁ -C ₄ alkyl;
R ₃₇ is C ₁ -C ₄ alkyl, C ₁ -C ₄ halogenalkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C ₄ halogen alkoxy-C _1. it is -C ₄ alkyl; and R ₃₈ represents hydrogen, halogen or cyano);
Or A is A ₄

(Where R ₄₆ and R ₄₇ are independently of each other halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ halogen alkoxy, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C a ₄ -haloalkoxy -C ₁ -C ₄ alkyl), compounds of formula I according to claim 1. A is A _1, a compound of formula I according to claim 4. R ₁₆ is located at C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkyl; R ₁₇ is located at C ₁ -C ₄ alkyl; and R ₁₈ is hydrogen or halogen, the formula I according to claim 5 Compound. A is a 6-membered heterocycle or phenyl ring containing 1 to 3 heteroatoms independently selected from oxygen, nitrogen and sulfur; said phenyl ring or heterocycle is a group R ₆ , R ₇ and R ₈ 2. A compound of formula I according to claim 1, which is substituted by: A is A ₅

(In the above formula,
R ₅₆ is halogen, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ -haloalkoxy or C ₁ -C ₄ -haloalkoxy -C ₁ -C ₄ alkyl);
Or A is A ₆

(In the above formula,
R ₆₆ is halogen, cyano, nitro, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogen alkyl, C ₁ -C ₄ alkoxy-C ₁ -C ₄ alkyl or C ₁ -C ₄ halogen alkoxy-C ₁ -C ₄ alkyl);
Or A is A ₇

(In the above formula,
R ₇₆ is C ₁ -C ₄ alkyl or C ₁ -C ₄ halogenalkyl).
8. A compound of formula I according to claim 7. R ₄ is C ₃ -C ₇ cycloalkyl acetynyl, phenyl acetynyl or halogenphenyl acetynyl, compounds of formula I according to claim 1. Q is Q _1A-1

(In the above formula,
R ₃ is halogen or C ₁ -C ₄ halogenalkyl; R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl, halogen phenyl acetylinyl or halogen phenyl; and R ₅ is hydrogen, halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogenalkyl, phenyl, halogen phenyl, C ₃ -C ₇ cycloalkyl acetynyl, phenyl acetynyl or halogenphenyl acetynyl)
14. A compound of formula I according to claim 13, wherein Q is Q _1B-1

(In the above formula,
R ₃ is halogen or C ₁ -C ₄ halogenalkyl; R ₄ is C ₃ -C ₇ cycloalkyl acetylinyl, phenyl acetylinyl, halogen phenyl acetylinyl or halogen phenyl; and R ₅ is hydrogen, halogen, C ₁ -C ₄ alkyl, C ₁ -C ₄ halogenalkyl, phenyl, halogen phenyl, C ₃ -C ₇ cycloalkyl acetynyl, phenyl acetynyl or halogenphenyl acetynyl)
The compound of formula I according to claim 1, wherein _2. A compound of formula I according to claim 1, wherein Q is Q2.   A method for controlling or preventing useful plants by phytopathogenic microorganisms, comprising a compound of formula I according to claim 1 or a composition comprising this compound as an active ingredient in a plant, a part thereof or a part thereof. A method comprising applying to a site.   A composition for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I according to claim 1 and an inert carrier.